Muscle cramps are not uncommon complications of hemodialysis (HD) treatments and lead to early termination of HD sessions and are therefore a significant cause of under-dialysis. The etiology of cramps in dialysis patients remains a matter of debate. Many reports suggested that vitamin E (vit. E) may be effective for the prevention of HD-associated cramps. We decided to perform a selected controlled trial of supplementary vit. E for treatment of patients on HD who experience frequent attacks during and between HD sessions. The goal was to compare the number of attacks of muscle cramps with the patient's baseline over a specific period of time. In this study, 19 HD patients were randomly selected of different age groups and ethnicity. Patient must have had at least 60 attacks of muscle cramps during and between HD sessions over a 12-week period. All selected patients received vit. E at a dose of 400 international units daily for 12 weeks, and the number of attacks of muscle cramps was recorded. The frequency of muscle cramps decreased significantly during vit. E therapy, and, at the end of the trial, vit. E led to cramp reductions of 68.3%. The reduction in number of attacks of muscle cramps had no significant correlation with age, sex, etiology of end-stage renal disease, serum electrolytes, or HD duration, and it showed a statistically positive correlation (P = 0.0001) with vit. E therapy. No vit. E-related adverse effects were encountered during the trial. Short-term treatment with vit. E is safe and effective in reducing number of attacks of muscle cramps in HD patients, as shown in our study.